I. Steric and Electrostatic Repulsions in the Inhibition of α-Chymotrypsin Catalysed Hydrolyses by Indole Derivatives. II. Steric Requirements for Substrates of α-Chymotrypsin

Year: 1961 DOI: 10.7907/YTFM-K212
The enzyme-inhibitor dissociation constants, i.e., KI's, were evaluated for the six isomeric pairs of C-substituted indolecarboxylate ions and carboxamides. The variation of KI with the position and nature of the substituent indicates that the enzyme-indole complex exhibits a high degree of steric hindrance near the 4 position of the indole ring and electrostatic repulsion due to a negative group near the indole nitrogen.

The synthesis of D,L-β,β-dimethylphenylalanine was modified by use of air oxidation of 4, 6-di-(α,α-dimethylbenzyl)pyrogallol to 3,5-di-(α,α-dimethylbenzyl)coumalic acid and permanganate oxidation of this product to obtain α-keto-β-phenylisovaleric acid. The by-products of the air oxidation were investigated.

D,L-2,6-Dimethyltyrosine, a previously unreported amino acid, and several of its derivatives were synthesized.

Studies on the rates of α-chymotrypsin catalysed hydrolyses of N-acetyl-D,L-t-leucine methyl ester, N-acetyl-D,L-β,β;-dimethyl-phenylalanine methyl ester and N-acetyl-D,L-2,6-dimethyltyrosine methyl ester indicate the presence of a strong β steric effect.

Methods of resolution of D,L-β,β-dimethylphenylalanine and D,L-2,6-dimethyltyrosine derivatives were investigated.

Methyl indole-2-carboxylate is not a substrate of α-chymotrypsin.